Chemically, omeprazole is 5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridinyl)-methyl]sulfinyl]-1H-benzimidazole. Omeprazole and therapeutically acceptable salts thereof are described in U.S. Pat. No. 4,255,431. Certain specific alkaline salts of omeprazole are disclosed in U.S. Pat. No. 4,738,974. Omeprazole is transformed into an effective inhibitor of gastric acid secretion in mammals, and is therefore useful as an anti-ulcer agent. Omeprazole may be used to prevent and/or treat gastric acid related disorders and gastrointestinal inflammatory diseases in mammals. In man, for example, omeprazole may be used to prevent and/or treat gastritis, gastric ulcer and duodenal ulcer.
Omeprazole is a racemic mixture of its two single enantiomers, the (R)- and (S)-enantiomer of omeprazole. These enantiomers are commonly referred to as (R)-omeprazole and (S)-omeprazole, respectively. The enantiomer, (S)-omeprazole, is commonly referred to as esomeprazole.
WO 94/27988 discloses certain salts of the single enantiomers of omeprazole and their preparation. These compounds are described as having improved pharmacokinetic properties which give an improved therapeutic profile, such as a lower degree of variation between individuals taking the compound.
WO 96/02535 discloses a process for preparing the single enantiomers of omeprazole and salts thereof. WO 98/54171 discloses a process for the preparation of the trihydrate of the magnesium salt of (ES)-omeprazole.
Esomeprazole, like many other similar benzimidazole compounds, is not stable in its free form and is susceptible to degradation in acid and neutral media. It has been found that alkali metal or alkaline earth metal salts of esomeprazole are more stable during storage than the corresponding neutral form.
U.S. Pat. No. 5,714,505 describes alkaline salts of the (-) enantiomer of 5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridiniyl)methyl]sulfinyl]-1H-benzimidazoles (i.e., esomeprazole) including the magnesium salt, which are used for inhibiting gastric acid secretion. Esomeprazole magnesium is prepared according to Examples 5, 6, and 7 of the '505 patent in optically pure crystalline form by precipitation/crystallization.
U.S. Pat. No. 6,124,464 discloses another process for preparing crystalline esomeprazole magnesium. U.S. Pat. No. 6,369,085 discloses three different types of crystalline esomeprazole magnesium viz. dihydrate form A, dihydrate form B and the trihydrate form. However, the inventors are not aware of any disclosure of an amorphous form of esomeprazole salts, including amorphous esomeprazole magnesium, in the prior art. It is known that different morphs of biologically active compounds may have different absorption profile in vivo and consequently different pharmacokinetic profile.